Nasopharyngeal carcinoma (NPC) is a malignancy that is prevalent among
populations from Southeast Asia. The carcinogenesis of NPC is thought to
be a multistep process involving several genetic changes. Our previous
study based on distance and branching-tree models for NPC carcinogenesis
indicated +12p11-p12 was an early event and should play an important role
in NPC development. To understand the role of +12p11-p12 as the tree model
predicted and evaluate which gene located at 12p11-p12 might be involved
in NPC development, semiquantitative RT-PCR was applied to examine the
expression status of 18 genes selected from 12p11-p12 in 36 NPC and 8 normal
nasopharynx (NP) biopsies. The results revealed that BCAT1, KCNJ8, PTX1,
and KRAS2 genes were overexpressed in NPC tissues and BCAT1
was of particular interest based on its function reported in other tumors.
To further elucidate the function of BCAT1 gene in NPC, BCAT1
expression was specifically suppressed in 5-8F NPC cell line by RNA interference
(RNAi), confirmed by RT-PCR and Western blotting. As expected, the depletion
of BCAT1 could effectively block the proliferation of NPC cells.
The BCAT1 identified in the amplified 12p11-p12 region may play
a certain role in NPC development.

Conjugation of anticancer drugs with different carriers has been extensively
studied recently as a potential method of obtaining improved drug forms.
The conjugation often results in the increase of the therapeutic effect,
alteration of a toxicity profile, and/or selective targeting of therapeutic
agent to the tissue of interest. We have synthesized mannan-methotrexate
conjugate by means of methotrexate anhydride and studied its antitumor
properties both in vitro and in vivo in comparison with free methotrexate.
Mannan-methotrexate conjugate showed significantly improved antitumor activity
compared to free methotrexate in the model of P388 mouse leukemia disseminated
in the peritoneal cavity treated with intraperitoneally injected chemotherapy.
Conversely, the antitumor effects of free methotrexate and mannan-methotrexate
conjugate were comparable when leukemia was implanted subcutaneously and
chemotherapy agents were administered intravenously. These results suggest
that mannan-methotrexate conjugate should be further investigated as a
potential therapeutic agent for intraperitoneally disseminated tumors.

Head and neck cancer (HNC) is a serious health problem worldwide and
tobacco smoke is a main causative factor for this malignancy. Interindividual
genetic differences in enzymes involved in the metabolism of tobacco smoke
carcinogens are one of the most important risk factors in the development
of HNC. GSTM1 and GSTT1 enzymes participate in detoxifying of tobacco smoke
carcinogens and have deletion polymorphisms. We performed a case control
study to investigate a possible association between GSTM1 and GSTT1
variants and HNC risk. A total of 98 HNC cases, all of which were squamous
cell carcinoma, and 120 healthy controls were investigated. GSTM1 and
GSTT1
polymorphisms were genotyped using PCR. There was a significant association
between HNC and GSTM1-null genotype (adjusted OR: 2.36, 95% CI:
1.303-4.26, p = 0.005). The frequency overall of GSTT1-null
genotypes was not significant in HNC patients compared with that of GSTT1-positive
genotypes (adjusted OR: 1.16, 95% CI: 0.563-2.397, p = 0.686). No
combined effect was observed for GSTM1 and GSTT1 genotypes.
When data were stratified by smoking status, cases having GSTM1-null
genotype who were smokers conferred the highest risk (adjusted OR: 4.06,
95% CI: 1.3-12.63). Thus, our results suggest that GSTM1 polymorphism
may significantly increase the risk of HNC and there is an additive interaction
between GSTM1-null genotype and smoking on HNC risk.

Department of Obstetrics and Gynecology, Graduate School of Medicine,
The University of Tokyo, Tokyo 113-8655, Japan

Mutation of neoplastic tumor suppressor genes, scribble, discs
large, and lethal giant larvae (lgl), causes disruption
of cell polarity and overproliferation of Drosophila epithelial
cells and neuroblasts. Reduced expression of human homologue of lgl,
Hugl-1,
has been reported to be involved in development and progression of human
colon cancer and malignant melanoma. To explore the association between
Hugl-1 expression and clinical character in endometrial cancer,
we examined the expression of Hugl-1 in primary endometrial cancer
tissues. The expression of Hugl-1 mRNA in 86 primary endometrial
cancer tissues was examined using semiquantitative reverse transcription
polymerase chain reaction (RT-PCR). All samples were categorized into two
groups: Hugl-1 positive and Hugl-1 negative. Clinical data
of each group were analyzed by Fisher's exact probability test and survival
rates of each group were compared by Kaplan-Meier method and Log-rank test.
Loss of Hugl-1 expression had correlation with the higher incidence
of lymph node metastasis, but not to the patient's age at onset, distant
metastasis, clinical stage, lymph or venous vessel invasion, or histopathological
grade of differentiation. The Hugl-1-positive group had poorer prognosis
compared with the Hugl-1-negative group. These results indicate
that loss of Hugl-1 expression in endometrial cancer may contribute
to lymph node metastasis and it can be a factor of poor prognosis.

Phase I enzyme CYP1A1 metabolizes environmental carcinogens and a Msp1
T/C functional polymorphism in 3´UTR in its gene has been reported
to influence the inducibilty of the enzyme. There are controversies regarding
association of the polymorphism with risk of esophageal cancer in Chinese
and Caucasian populations. Moreover, no study has been done in Indian populations.
The present study was aimed to explore the associations of CYP1A1 3´UTR
polymorphism with clinical phenotypes and environmental interaction in
esophageal cancer from North Indian population. A total of age- and gender-matched
161 cases and 201 healthy controls were used to genotype the CYP1A1
3´UTR polymorphism by PCR-EFLP methodology. None of the CYP1A1
genotypes and alleles was significantly associated with risk of esophageal
cancer, even after adjusting for age and sex. After stratifying the genotypes
according to disease characteristics such as tumor histology, location,
and lymph nodes, individuals with TT genotype were at high risk
for developing tumor in the upper third location (OR: 2.2, 95% CI: 0.81-6.2,
p = 0.11). Interaction of tobacco usage (smoking or nonsmoking)
and presence of occupational exposure in esophageal cancer patients did
not show significant increase in cancer risk with CYP1A1 genotypes.
However, in patients with alcohol habits, TT genotype showed a higher
risk, which was not significant (OR: 2.5, 95% CI: 0.61-10.6, p =
0.19). In conclusion, CYP1A1 genotype did not influence the susceptibility
of developing esophageal cancer. The presence of variant CYP1A1 genotypes
together with environmental exposures also did not modulate the cancer
risk.

Department of Lung Diseases and Tuberculosis, Medical University of
Bialystok, Bialystok, Poland

The aim of this study was to assess serum levels of vascular endothelial
growth factor C and D (VEGF-C, VEGF-D) and soluble VEGF receptor 2 (sVEGFR-2)
in patients with lung cancer during chemotherapy. The study included 80
patients (64 men and 16 women; mean age 61.1) diagnosed histologically
with lung cancer. Forty-four (55%) had non-small cell lung cancer (NSCLC)
and 36 (45%) had small cell lung cancer (SCLC). Squamous cell carcinoma
was established in 56% (25 patients) of all patients with NSCLC, adenocarcinoma
in 20% (9 patients), and non-small cell lung cancer in 23% (10 patients).
The control group consisted of 20 healthy volunteers. Peripheral blood
samples were taken before and after four cycles of chemotherapy. VEGF-C,
VEGF-D, and sVEGFR-2 levels were assessed by ELISA method. Serum levels
of VEGF-C and VEGF-D were significantly higher in both NSCLC and SCLC groups
in comparison with controls. VEGF-C concentration decreased after chemotherapy,
whereas VEGF-D concentration was at the same level. No correlation was
found between VEGF-C and VEGF-D concentrations and the effect of treatment.
Patients with lung cancer and progression after chemotherapy (PD) had the
higher concentration of sVEGFR-2 than patients with partial remission (PR).
The levels of sVEGFR-2 were lower before and after treatment than in controls.
No relation was found between VEGF-C, VEGF-D, and sVEGFR-2 concentrations
and the histological type and staging of lung cancer. Summing up, serum
concentrations of VEGFC and VEGF-D were higher in patients with lung cancer
both before and after chemotherapy than in healthy controls, whereas sVEGFR-2
concentration was lower than in healthy controls. An increase in concentration
of sVEGFR-2 during chemotherapy may suggest progression of the disease.
However, it requires further examination.